Abstract

BackgroundThe association of diabetic nephropathy (DN) risk with single nucleotide polymorphisms (SNPs) within Engulfment and Cell Motility 1 (ELMO1) gene and gene–environment synergistic effect have not been extensively examined in, therefore, the purpose of this study is to explore the association between multiple SNPs in ELMO1 gene, and the relationship between gene–environment synergy effect and the risk of DN.MethodsGenotyping for 4 SNPs was performed with polymerase chain reaction (PCR) and following restriction fragment length polymorphism (RFLP) methods. Hardy–Weinberg balance of the control group was tested by SNPstats (online software: http://bioinfo.iconologia.net/snpstats). The best combination of four SNPs of ELMO1 gene and environmental factors was screened by GMDR model. Logistic regression was used to calculating the OR values between different genotypes of ELMO1 gene and DN.ResultsThe rs741301-G allele and the rs10255208-GG genotype were associated with an increased risk of DN risk, adjusted ORs (95% CI) were 1.75 (1.19–2.28) and 1.41 (1.06–1.92), respectively, both p-values were < 0.001. We also found that the others SNPs-rs1345365 and rs7782979 were not significantly associated with susceptibility to DN. GMDR model found a significant gene–alcohol drinking interaction combination (p = 0.0107), but no significant gene–hypertension interaction combinations. Alcohol drinkers with rs741301-AG/GG genotype also have the highest DN risk, compared to never drinkers with rs741301-AA genotype, OR (95% CI) 3.52 (1.93–4.98).ConclusionsThe rs741301-G allele and the rs10255208-GG genotype, gene–environment interaction between rs741301 and alcohol drinking were all associated with increased DN risk.

Highlights

  • The association of diabetic nephropathy (DN) risk with single nucleotide polymorphisms (SNPs) within Engulfment and Cell Motility 1 (ELMO1) gene and gene–environment synergistic effect have not been extensively examined in, the purpose of this study is to explore the association between multiple SNPs in ELMO1 gene, and the relationship between gene–environment synergy effect and the risk of DN

  • Diabetic nephropathy (DN) is one of the most destructive microvascular complications of all the complications of diabetes, and it is the main cause of end-stage renal disease (ESRD), which accounts for a large proportion of the morbidity and mortality of diabetes [1]

  • We found a significant gene–alcohol drinking interaction combination, but no significant gene–hypertension interaction combinations, after adjusting for age, gender, BMI, smoking and alcohol drinking covariates

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Summary

Introduction

The association of diabetic nephropathy (DN) risk with single nucleotide polymorphisms (SNPs) within Engulfment and Cell Motility 1 (ELMO1) gene and gene–environment synergistic effect have not been extensively examined in, the purpose of this study is to explore the association between multiple SNPs in ELMO1 gene, and the relationship between gene–environment synergy effect and the risk of DN. Genome-Wide Association Studies (GWAS) and metaanalysis [6, 7] have reported some genes related with susceptibility to DN in different populations. In 2005, a Japanese GWAS study [8] confirmed that Engulfment and Cell Motility 1 (ELMO1) gene is a new candidate gene. In this study, they evaluated more than 80,000 loci and found that one SNP locus in intron 18 of ELMO1 gene was closely related to DN. The present study aimed to evaluate the impact of four SNPs in the ELMO1 gene, and its interaction with environmental risk factors on susceptibility to DN

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